Abstract
Hydrogels are broadly employed in wound healing applications due to their high water content and tissue-mimicking mechanical properties. Healing is hindered by infection in many types of wound, including Crohn's fistulas, tunneling wounds that form between different portions of the digestive system in Crohn's disease patients. Owing to the rise of drug-resistant infections, alternate approaches are required to treat wound infections beyond traditional antibiotics. To address this clinical need, we designed a water-responsive shape memory polymer (SMP) hydrogel, with natural antimicrobials in the form of phenolic acids (PAs), for potential use in wound filling and healing. The shape memory properties could allow for implantation in a low-profile shape, followed by expansion and would filling, while the PAs provide localized delivery of antimicrobials. Here, we developed a urethane-crosslinked poly(vinyl alcohol) hydrogel with cinnamic (CA), p-coumaric (PCA), and caffeic (Ca-A) acid chemically or physically incorporated at varied concentrations. We examined the effects of incorporated PAs on antimicrobial, mechanical, and shape memory properties, and on cell viability. Materials with physically incorporated PAs showed improved antibacterial properties with lower biofilm formation on hydrogel surfaces. Both modulus and elongation at break could be increased simultaneously in hydrogels after both forms of PA incorporation. Cellular response in terms of initial viability and growth over time varied based on PA structure and concentration. Shape memory properties were not negatively affected by PA incorporation. These PA-containing hydrogels with antimicrobial properties could provide a new option for wound filling, infection control, and healing. Furthermore, PA content and structure provide novel tools for tuning material properties independently of network chemistry, which could be harnessed in a range of materials systems and biomedical applications.